The overall objective of the project is to ascertain the molecular details of certain basic structural elements of nucleic acids and answer important questions about their stability and mode of interaction with other biologically important molecules. Oligomeric components of larger nucleic acids are enzymically synthesized and their conformation and stability studied by nuclear magnetic resonance and optical spectroscopy throughout an order-disorder transition induced by temperature, ionic strength, or interaction with some other molecule. The form and stability of the natural counterparts of the synthetic structures will be inferred from these physical properties in aqueous solution. These investigations should yield a wide variety of information applicable to understanding the function of natural nucleic acids. Due to recent advances in techniques for sequencing DNA and RNA there is tremendous interest in ascertaining the correct 3-dimensional folding of natural nucleic acids. Our studies of basic elements of nucleic acid structure and the dependence of their structure and stability on sequence should allow us to predict appropriate folded structures of natural nucleic acids based upon their sequence. Further, such a solid background of information will simplify the interpretation of studies on the interaction of nucleic acids with other biologically important molecules such as drugs and mutagenic compounds.